Prostate cancer (PCa) is a malignant tumor that occurs in the prostate tissue of males, and is the result of abnormal disordered growth of prostate acinar cells. The differentiation and growth of normal prostate epithelial cells as well as the development of prostate cancer all depend on androgen that is mainly (about 80-90%) synthesized in testis. Synthetic androgen binds to the androgen receptor (AR) after entering the cells, and causes the dissociation of heat shock protein (HSP) from the AR, then the AR enters the nucleus and activates multiple downstream genes, including prostate-specific antigen (PSA). Early prostate cancer is sensitive to androgen, orchiectomy (castration) thus can significantly inhibit the development of prostate cancer. However, the castration surgery is effective for a certain period of time, and many patients undergo the transformation from androgen-dependent to androgen-independent within a period of time after castration. The prostate cancer of these patients develops into the androgen independent prostate cancer (AIPC), and the anti-androgen therapy is no longer effective to them. The occurrence of AIPC still has an important relationship with the activation of AR signaling pathway in PCa cells.
The first-generation drugs, which aim at inhibiting AR activity, include Bicalutamide (or Casodex) and Flutamide. The second-generation AR antagonist drugs for AIPC therapy include MDV3100 and ARN-509. MDV3100 is the first second-generation non-steroidal AR antagonist drug in the world, and was approved by the FDA at the end of August 2012. The affinity of MDV-3100 to AR is 5-8 times higher than that of bicalutamide. MDV-3100 can inhibit the growth of AIPC in mouse and human by inhibiting AR activity, and has no effect of promoting tumor cell growth.

WO2014036897A1 discloses novel AR antagonists, including a compound of formula (I), with a chemical name of (S)-4-(3-(4-(2,3-dihydroxypropoxy)phenyl)-4,4-dimethyl-5-carbonyl-2-thioimidazolin-l-yl)-2-(trifluoromethyl)benzonitrile. The activity in vitro of this compound is slightly better than that of MDV-3100, and the hERG inhibition rate is further improved (IC50: 24.83 μM). The inhibition half lives of this compound on five major subtypes of CYP450 are all greater than 50 μM. The in vivo exposure of this compound in rats is comparable to that of MDV-3100, and the in vivo exposure of this compound in dogs is more than six times that of MDV-3100, at the same dose and in the same solvent. The compound of formula (I) has only one chiral center. The chiral starting material is easy to obtain, and the synthesis difficulty is greatly reduced. In addition, the compound of formula (I) has no AR agonist activity at 3 μM and 10 μM, and the ratio of the drug concentration in brain tissue to the drug concentration in plasma in mice is much lower than that of MDV-3100 compound, and so the possibility of epileptic side effects is smaller. Therefore, the compound of formula (I) has a broad clinical prospect.

However, the above-mentioned document does not disclose how to obtain a stable pharmaceutical composition comprising the above-mentioned compound and the dissolution rate which meets the requirement. Studies have found that the above-mentioned compound has poor stability, and some conventional formulations cannot guarantee the stability of the composition; meanwhile, the compound is poorly soluble in a lot of compositions prepared with conventional auxiliaries. Therefore, in-depth studies are required to find a stable composition with a good dissolution rate.